|
1
|
Ferreira-da-Silva R, Reis-Pardal J, Pinto M, Monteiro-Soares M, Sousa-Pinto B, Morato M, Polónia JJ, Ribeiro-Vaz I. A Comparison of Active Pharmacovigilance Strategies Used to Monitor Adverse Events to Antiviral Agents: A Systematic Review. Drug Saf 2024; 47:1203-1224. [PMID: 39160354 PMCID: PMC11554745 DOI: 10.1007/s40264-024-01470-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2024] [Indexed: 08/21/2024]
Abstract
INTRODUCTION The safety of antiviral agents in real-world clinical settings is crucial, as pre-marketing studies often do not capture all adverse events (AE). Active pharmacovigilance strategies are essential for detecting and characterising these AE comprehensively. OBJECTIVE The aim of this study was to identify and characterise active pharmacovigilance strategies used in real-world clinical settings for patients under systemic antiviral agents, focusing on the frequency of AE and the clinical data sources used. METHODS We conducted a systematic review by searching three electronic bibliographic databases targeting observational prospective active pharmacovigilance studies, phase IV clinical trials for post-marketing safety surveillance, and interventional studies assessing active pharmacovigilance strategies, focusing on individuals exposed to systemic antiviral agents. RESULTS We included 36 primary studies, predominantly using Drug Event Monitoring (DEM), with a minority employing sentinel sites and registries. Human immunodeficiency virus (HIV) was the most common condition, with the majority using DEM. Within the DEM, there was a wide range of incidences of patients experiencing at least one AE, and most of these studies used one or two data sources. Sentinel site studies were less common, with two on hepatitis C virus (HCV) and one on HIV, each relying on one or two data sources. The single study using a registry focusing on HIV therapy reported using just one data source. Patient interviews were the most common data source, followed by medical records and laboratory tests. The quality of the studies was considered 'good' in 18/36, 'fair' in 1/36, and 'poor' in 17/36 studies. CONCLUSION DEM was the predominant pharmacovigilance strategy, employing multiple data sources, and appears to increase the likelihood of detecting higher AE incidence. Establishing such a framework would facilitate a more detailed and consistent approach across different studies and settings.
Collapse
Affiliation(s)
- Renato Ferreira-da-Silva
- Porto Pharmacovigilance Centre, Faculty of Medicine of the University of Porto, Porto, Portugal.
- Center for Health Technology and Services Research, Associate Laboratory RISE-Health Research Network (CINTESIS@RISE), Porto, Portugal.
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.
| | - Joana Reis-Pardal
- Center for Health Technology and Services Research, Associate Laboratory RISE-Health Research Network (CINTESIS@RISE), Porto, Portugal
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
| | - Manuela Pinto
- São João University Hospital Centre, Porto, Portugal
| | - Matilde Monteiro-Soares
- Center for Health Technology and Services Research, Associate Laboratory RISE-Health Research Network (CINTESIS@RISE), Porto, Portugal
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
- Portuguese Red Cross Health School-Lisbon, Lisbon, Portugal
- Cross I&D, Lisbon, Portugal
| | - Bernardo Sousa-Pinto
- Center for Health Technology and Services Research, Associate Laboratory RISE-Health Research Network (CINTESIS@RISE), Porto, Portugal
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
| | - Manuela Morato
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of the University of Porto, Porto, Portugal
- LAQV@REQUIMTE, Faculty of Pharmacy of the University of Porto, Porto, Portugal
| | - Jorge Junqueira Polónia
- Porto Pharmacovigilance Centre, Faculty of Medicine of the University of Porto, Porto, Portugal
- Center for Health Technology and Services Research, Associate Laboratory RISE-Health Research Network (CINTESIS@RISE), Porto, Portugal
- Department of Medicine, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Inês Ribeiro-Vaz
- Porto Pharmacovigilance Centre, Faculty of Medicine of the University of Porto, Porto, Portugal
- Center for Health Technology and Services Research, Associate Laboratory RISE-Health Research Network (CINTESIS@RISE), Porto, Portugal
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal
| |
Collapse
|
|
2
|
Pan CQ, Afdhal NH, Ankoma‐Sey V, Bae H, Curry MP, Dieterich D, Frazier L, Frick A, Hann H, Kim WR, Kwo P, Milligan S, Tong MJ, Reddy KR. First-line therapies for hepatitis B in the United States: A 3-year prospective and multicenter real-world study after approval of tenofovir alefenamide. Hepatol Commun 2022; 6:1881-1894. [PMID: 35445803 PMCID: PMC9315121 DOI: 10.1002/hep4.1964] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 03/01/2022] [Accepted: 03/04/2022] [Indexed: 12/28/2022] Open
Abstract
Real-world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real-world outcomes with other first-line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen-negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR < 60 ml/mi/1.7 m2 was observed in the TDF-treated group (9% vs. 4%; p = 0.010). In patients who remained on entecavir or TDF for 24 months, ALT and HBV-DNA results did not differ significantly from baseline. Treatment of CHB in the United States has significantly shifted from TDF to TAF. Our data suggest that switching from TDF or entecavir to TAF may result in increased frequency of ALT normalization and potential clearance of viremia at the 24-month time point.
Collapse
Affiliation(s)
- Calvin Q. Pan
- Beijing Ditan HospitalCapital Medical UniversityBeijingChina
- NYU Langone HealthNYU Grossman School of MedicineNew YorkNew YorkUSA
| | | | | | - Ho Bae
- St. Vincent Medical CenterAsian Pacific Liver CenterLos AngelesCaliforniaUSA
| | | | | | | | | | - Hie‐Won Hann
- Thomas Jefferson University HospitalPhiladelphiaPennsylvaniaUSA
| | - W. Ray Kim
- Stanford University School of MedicineStanfordCaliforniaUSA
| | - Paul Kwo
- Stanford University School of MedicineStanfordCaliforniaUSA
| | | | - Myron J. Tong
- Huntington Medical Research InstitutesPasadenaCaliforniaUSA
| | | |
Collapse
|
|
3
|
Cho EJ, Yu SJ, Kwon SY, Kim JH, Kim DY, Kim W, Lee JS, Lee JW, Lee YJ, Chae HB, Yoon JH. Concomitant food intake does not affect the efficacy of entecavir in chronic hepatitis B patients with virological response: a randomized, multicenter, noninferiority trial. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:3767-3774. [PMID: 30464407 PMCID: PMC6223329 DOI: 10.2147/dddt.s181561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Background Little clinical data are available about the effect of food on the antiviral efficacy of entecavir for chronic hepatitis B virus (HBV) infection. The present study evaluated whether entecavir administration in the fed state had comparable efficacy to the fasted condition for maintenance of viral suppression in HBV-infected patients with virological response on entecavir therapy. Methods In this multicenter, randomized, open-label, noninferiority study, patients who were currently receiving entecavir and showed a serum HBV DNA level of <20 IU/mL were randomized to take entecavir either under the fasted or fed condition for 48 weeks. Results We randomly assigned 50 patients to the fasted group and 46 patients to the fed group. The full analysis set consisted of 49 patients in the fasted group and 44 patients in the fed group. At week 48, the proportion of patients with HBV DNA <20 IU/mL was not significantly different between the fasted and fed groups (98% vs 100%, P=1.00). The mean log10 HBV DNA changes from baseline were similar between the two groups (−0.004 vs −0.012 log10 IU/mL, P=0.43). There were no significant differences in the proportions of patients with normal alanine aminotransferase (87.8% vs 95.5%, P=0.27) and hepatitis B e-antigen seroconversion (0% vs 6.7%, P=0.47) between the two groups. None of the patients showed viral breakthrough. In pharmacokinetic analysis, the maximum concentration and the area under the concentration– time curve to the last quantifiable concentration decreased by 26.4% and 9.3%, respectively, in the fed group compared with the fasted group. However, the differences between two groups were not statistically significant (P=0.28 and 0.83, respectively). Conclusion In patients with virological response under entecavir therapy, concomitant food intake did not affect the antiviral efficacy. For patients with adherence problem, taking entecavir with food may be considered to improve compliance.
Collapse
Affiliation(s)
- Eun Ju Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea,
| | - Su Jong Yu
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea,
| | - So Young Kwon
- Department of Internal Medicine, Konkuk University School of Medicine, KonKuk University Hospital, Seoul, South Korea
| | - Ji-Hoon Kim
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea
| | - June Sung Lee
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
| | - Jin Woo Lee
- Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Youn Jae Lee
- Department of Gastroenterology, Inje University Busan Paik Hospital, Busan, South Korea
| | - Hee Bok Chae
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea,
| |
Collapse
|